The proposed work involves two separate categories of compounds-diagnostic agents and weak analgesics: 1) To examine the role of plasma protein binding of cholegraphic agents in the isolated perfused rat liver to determine to what extent biliary excretion depends on the concentration of free and protein-bound compounds; 2) To determine the role of pKa for organic acid uptake in the kidney cortex organic acid secretory mechanism; and 3) To evaluate inhibition of organic acid uptake as an index of nephrotoxicity. Our work on weak analgesics is an outgrowth of our previous studies on the renal response to acute diuresis during the course of intravenous pyelography. We propose to continue our studies on the renal excretion of trace metabolites of phenacetin and acetaminophen and to determine their intra-renal distribution. BIBLIOGRAPHIC REFERENCES: Analgesic nephropathy: renal distribution of acetaminophen and its conjugates. G.G. Duggin and G.H. Mudge. J. Pharm. Exp. Therap. 199: 1-9, 1976. Phenacetin: Renal tubular transport and intrarenal distribution in the dog. G.G. Duggin and G.H. Mudge. J. Pharm. Exp. Therap. 199: 10-16, 1976.